Inclusion Criteria:

          -  Advanced colorectal cancer (metastatic or unresectable): Histologically or cytological
             proven adenocarcinoma of the colon or rectum which is metastatic or otherwise
             incurable

          -  Prior treatment with a fluoropyrimidine (5-fluorouracil [5-FU] or capecitabine) and
             oxaliplatin in the metastatic/unresectable setting OR, recurrence within 12 months of
             adjuvant therapy with a regimen that included oxaliplatin

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Hemoglobin >= 9 g/dL

          -  Absolute neutrophil count >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Creatinine < 1.5 upper limit of normal (ULN) or if >= 1.5 x ULN creatinine clearance
             (CRCL) >= 30 mL/min (by Cockcroft-Gault)

          -  Bilirubin < 1.5 x ULN

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5 x
             ULN if with hepatic metastases

          -  Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
             criteria present

          -  Participants of child-bearing potential must agree to use adequate contraceptive
             methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
             entry. Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately

          -  Participant must understand the investigational nature of this study and sign an
             Independent Ethics Committee/Institutional Review Board approved written informed
             consent form prior to receiving any study related procedure

        Exclusion Criteria:

          -  Prior treatment with TAS-102 or irinotecan

          -  Anti-cancer therapy within 2 weeks of the planned first dose of study medication

          -  Unresolved toxicities from prior therapy of > grade 1, excluding alopecia or similar
             toxicities which are not deemed to be clinically significant or put the participant at
             greater risk. Grade 2 neuropathy is permitted

          -  Major surgery within 4 weeks of anticipated start of therapy

          -  Uncontrolled hypertension: systolic blood pressure >= 150, diastolic blood pressure >=
             100

          -  Unstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring
             anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are
             allowed)

          -  Arterial or venous thrombotic or embolic events within 3 months of study initiation,
             unless well controlled on stable anti-coagulation for >= 2 weeks. This excludes
             uncomplicated catheter associated venous thrombosis

          -  History of cerebrovascular or myocardial ischemia within 6 months of initiation

          -  National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
             version (v) 5.0 grade 3 or greater hemorrhage within the past 4 weeks

          -  Proteinuria >= 2+, unless 24 hour urine collection demonstrates =< 1 g of protein OR
             spot protein: creatinine demonstrates a ratio of =< 1

          -  Untreated brain metastases

          -  History of abnormal glucuronidation of bilirubin (Gilbert's syndrome)

          -  History of second primary malignancy within 3 years prior to enrollment, excluding
             in-situ cervical carcinoma, non-melanoma skin cancer or malignancy of equivalent risk
             which is highly unlikely to require systemic treatment in the next 2 years

          -  Have known active infection which would heighten the risk of complications

          -  Pregnant or nursing female participants

          -  Unwilling or unable to follow protocol requirements

          -  Any condition which in the investigator's opinion deems the participant an unsuitable
             candidate to receive study drug