Inclusion Criteria:

          -  Signed informed consent obtained before any study specific procedures

          -  Male or female ≥ 18 years of age

          -  Histological documentation of adenocarcinoma of the colon or rectum

          -  Patients with metastatic colorectal cancer

          -  Progression during or within 3 months following the last administration of approved
             standard therapies, which must include a fluoropyrimidine (or raltitrexed),
             oxaliplatin, irinotecan, anti VEGF therapy and an anti EGFR therapy (for RAS wild-type
             tumors)

          -  ECOG performance status ≤1

          -  Life expectancy of at least 3 months

          -  Patients with A/A CCND1 genotype of rs603965 CCND1

          -  Adequate bone marrow, liver and renal function as assessed by the following laboratory
             requirements conducted within 7 days of starting study treatment: Amylase and lipase
             ≤1.5 x ULN,Total bilirubin ≤ 1.5 x ULN,Alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x ULN for patients with liver involvement of
             their cancer), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with
             liver involvement for their cancer and/or have bone metastases), Platelet count ≥
             100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3.
             Transfusion to meet the inclusion criterion, Serum creatinine ≤ 1.5 x ULN

          -  International normalized ratio (INR) ≤ 1.5 x ULN and partialthromboplastin 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

          -  Women of childbearing potential must have a blood or urine pregnancy test performed a
             maximum of 7 days before start of study treatment, and a negative result must be
             documented before start of study treatment

          -  Women of childbearing potential and men must agree to use adequate contraception
             before entering the study until at least 8 weeks after the last study drug
             administration of Regorafenib and 12 weeks after the last study drug administration of
             Irinotecan. The investigator or a designated associate is requested to advise the
             patient on how to achieve an adequate birth control. Adequate contraception is defined
             in the study as any medically recommended method (or combination of methods) as per
             standard of care.

        Exclusion Criteria:

          -  Patients with A/G or G/G CCND1 genotype of rs603965 CCND1

          -  Prior treatment with regorafenib or sorafenib

          -  Prior treatment with TAS 102

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

          -  Pregnant or breast-feeding subjects. Women of childbearing potential must have a
             pregnancy test performed a maximum of 7 days before start of treatment, and a negative
             result must be documented before start of study drug

          -  Congestive heart failure ≥ New York Heart Association (NYHA) class 2

          -  Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
             months)

          -  Myocardial infarction less than 6 months before start of study drug

          -  Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are
             permitted)

          -  Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure >
             90 mmHg despite optimal medical management)

          -  Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE V5.0 Grade
             2 dyspnea)

          -  Ongoing infection > Grade 2 NCI-CTCAE V5.0

          -  Known history of human immunodeficiency virus (HIV) infection

          -  Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with
             antiviral therapy

          -  Patients with seizure disorder requiring medication

          -  History of organ allograft

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

          -  Any hemorrhage or bleeding event ≥ NCI-CTC V5.0 Grade 3 within 4 weeks prior to the
             start of study medication

          -  Non-healing wound, ulcer, or bone fracture

          -  Dehydration NCI-CTCAE V5.0 Grade ≥ 1

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the subject's participation in the study or evaluation of the study results

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

          -  Any illness or medical conditions that are unstable or could

          -  jeopardize the safety of the subject and his/her compliance in the study

          -  Persistent proteinuria of NCI-CTCAE V5.0 Grade 3 (> 3.5g/24 hours)

          -  Patients unable to swallow oral medications

          -  Any malabsorption condition

          -  Chronic inflammatory bowel disease and / or bowel obstruction

          -  Unresolved toxicity higher than NCI-CTCAE V.5.0 Grade 1 attributed to any prior
             therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced
             neurotoxicity ≤ Grade 2

          -  Concomitant participation or participation within the last 30 days in another clinical
             trial

          -  Systemic anticancer therapy during this trial or within 4 weeks before randomization

          -  Concomitant intake of st John's wort

          -  Live attenuated vaccines are prohibited 10 days before the treatment, during the
             treatment and 6 months after the termination of treatment

          -  History of gastrointestinal fistula or perforation

          -  Previous or concurrent cancer that is distinct in primary site or histology from
             colorectal cancer within 5 years prior to study inclusion, except for curatively
             treated cervical cancer in situ, non-melanoma skin cancer and superficial