Inclusion Criteria:

          -  Patients who provided written informed consent to be subjects in this trial

          -  Patients with histologically or cytologically confirmed advanced or metastatic
             colorectal cancer who had failed or are intolerant of oxaliplatin, irinotecan, and
             fluorouracil (5-FU)

          -  Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of
             0 or 1

          -  Patients capable of taking oral medication

          -  Patients with evaluable or measurable lesions as per Response Evaluation Criteria in
             Solid Tumors (RECIST) version 1.1

          -  Neutrophil count >= 200/mm^3

          -  Platelet count >= 7.5 x 10^4/mm^3 (transfusion > 2 weeks before testing permitted)

          -  Aspartate transaminase (AST), alanine transaminase (ALT) =< 2.5-times the upper limit
             of normal (=< 5-times in patients with liver metastasis)

          -  Total bilirubin =< 1.5-times the upper limit of normal

          -  Creatinine =< 1.5-times the upper limit of normal

          -  Lipase =< 1.5 x the upper limit of normal (ULN)

          -  International normalized ratio (INR) =< 1.5 x ULN and partial thromboplastin time
             (PTT) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless receiving
             treatment with therapeutic anticoagulation. Patients being treated with anticoagulant,
             e.g. heparin, will be allowed to participate provided no prior evidence of an
             underlying abnormality in these parameters exists. Close monitoring of at least weekly
             evaluations will be performed until INR and PTT are stable based on a pre-dose
             measurement as defined by the local standard of care

          -  In women with the potential for pregnancy (including patients with amenorrhea due to
             medical reasons, such as chemical menopause), after consenting to the study, the
             patient must agree to take contraception for at least 23 weeks after taking the final
             dose of the investigational drug (a period of 30 days [ovulation cycle] is added to
             five times the elimination half-time of I/O agent). Women with the potential for
             pregnancy include those who have begun menstruation, who have not undergone a
             hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, and who have not
             gone through menopause. Menopause is defined as the consecutive absence of menstrual
             periods for >= 12 months

          -  In the case of men, the patient must agree after consenting to the study to take
             contraception for at least 31 weeks after taking the final dose of the investigational
             drug (a period of 90 days [the spermatogenesis cycle] is added to five times the
             elimination half-time of immuno-oncology (I/O) agent

        Exclusion Criteria:

          -  Patients who have undergone systemic chemotherapy, radiotherapy, surgery, hormone
             therapy, or immunotherapy < 2 weeks before enrollment. Immune checkpoint blockade as
             pretreatment is permitted

          -  Patients with a history of taking regorafenib

          -  Patients with hypertension that is difficult to control (systolic blood pressure >=
             150 mmHg and diastolic blood pressure >= 90 mmHg) despite treatment with several
             hypotensive agents

          -  Patients with acute coronary syndrome (including myocardial infarction and unstable
             angina), and with a history of coronary angioplasty or stent placement performed
             within 6 months before enrollment

          -  Patients with a large amount of pleural effusion or ascites requiring more than weekly
             drainage

          -  Patients with a >= grade 3 active infection according to National Cancer Institute
             (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

          -  Patients with symptomatic brain metastasis

          -  Patients with partial or complete gastrointestinal obstruction

          -  Patients with interstitial lung disease with symptoms or signs of activity

          -  Patients who test positive for either anti-human immunodeficiency virus (HIV)-1
             antibodies, anti-HIV-2 antibodies, anti-human T-lymphotropic virus (HTLV)-1
             antibodies, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV)
             antibodies*

               -  Patients who test positive for either anti-hepatitis B surface antigen (HBs) or
                  anti-hepatitis B core antigen (HBc) antibodies, and those who have hepatitis B
                  virus (HBV)-deoxyribonucleic acid (DNA) measurements greater than the detection
                  sensitivity will also be excluded

          -  Patients with concurrent autoimmune disease, or a history of chronic or recurrent
             autoimmune disease

          -  Patients who require systemic corticosteroids (excluding temporary usage for tests,
             prophylactic administration for allergic reactions, or to alleviate swelling
             associated with radiotherapy) or immunosuppressants, or who have received such a
             therapy < 14 days before enrollment in the present study

          -  Patients with a history or findings of >= grade III congestive heart failure according
             to the New York Heart Association functional classification

          -  Patients with a seizure disorder who require pharmacotherapy

          -  Persistent proteinuria > 3.5 g/24 hours measured by urine protein-creatinine ratio
             from a random urine sample (>= grade 3, NCI-CTCAE version [v] 4.0)

          -  Known hypersensitivity to any of the study drugs, study drug classes, or excipients in
             the formulation

          -  Major surgical procedure or significant traumatic injury within 28 days before start
             of study medication

          -  Non-healing wound, non-healing ulcer, or non-healing bone fracture

          -  Patients with evidence or history of any bleeding diathesis, irrespective of severity

          -  Any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to the start of
             study medication

          -  Women who are pregnant or breastfeeding, or with the potential for pregnancy

          -  EXCLUDED THERAPIES AND MEDICATIONS, PREVIOUS AND CONCOMITANT

          -  Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
             immunotherapy, biologic therapy, or tumor embolization) other than study treatment
             (regorafenib and pembrolizumab)

          -  Concurrent use of another investigational drug or device therapy (i.e., outside of
             study treatment) during, or within 2 weeks of trial entry (signing of the informed
             consent form is OK in the washout period)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             before start of study medication

          -  Therapeutic anticoagulation with vitamin-K antagonists (e.g., warfarin) or with
             heparins and heparinoids. However, prophylactic anticoagulation as described below is
             allowed:

               -  Low dose warfarin (1 mg orally, once daily) with PT-INR =< 1.5 x ULN is
                  permitted. Infrequent bleeding or elevations in PT-INR have been reported in some
                  subjects taking warfarin while on regorafenib therapy. Therefore, subjects taking
                  concomitant warfarin should be monitored regularly for changes in PT, PT-INR or
                  clinical bleeding episodes

               -  Low dose aspirin (=< 100 mg daily)

               -  Prophylactic doses of heparin

          -  During the study, strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice,
             indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole,
             ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg,
             carbamazepine, phenobarbital, phenytoin, rifampin, St. John?s wort) are not permitted

          -  Live vaccines administered < 30 days before the initiation of treatment with the
             investigational drug and during the trial period. Examples of live vaccines are as
             follows (however, the list is not exhaustive): measles, mumps, rubella, chicken
             pox/herpes zoster, yellow fever, rabies, BCG for tuberculosis, and typhoid vaccines.
             Inoculation with inactive vaccines (e.g., seasonal influenza vaccines) is permitted;
             however, the intranasal administration of attenuated influenza vaccines (e.g.,
             Flu-Mist) is prohibited

          -  Systemic glucocorticoids for purposes other than treating symptoms caused by notable
             events with a suspected immunological etiology. Upon deliberation with the trial
             coordinating committee, the use of corticosteroids may be permitted according to the
             physiological dose required to alleviate symptoms (e.g., to control symptoms of acute
             asthma)