A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC

Inclusion Criteria:

1. Has provided written informed consent.
2. Participants with confirmed histologically proven metastatic or locally advanced colorectal adenocarcinoma who are microsatellite stable (MSS) (ie, not microsatellite instable \[MSI\]) based on either an analysis of tissue from a prior biopsy or based on tissue from a new biopsy.
3. Participants with the presence of at least 1 lesion with measurable disease as defined by 10 millimeters (mm) in the longest diameter for a soft tissue lesions or 15 mm in the short axis for a lymph node by response evaluation criteria in solid tumors (RECIST) and immune related response-criteria (irRC) for a response assessment.
4. Participants has received at least 2 prior lines of standard chemotherapies for metastatic colorectal cancer (mCRC) and is refractory to or failing those chemotherapies.
5. Age greater than or equal to (\>=) 18 years.
6. Eastern Cooperative Oncology Group performance status of 0 to 1
7. Life expectancy of \>=4 months.
8. Has adequate organ function.
9. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days before starting study drugs. Is able to take medications orally.
10. Is able to take medications "orally".

Exclusion Criteria:

1. Has a serious illness or medical condition.
2. Treatment with any of the following within the specified time frame before enrollment:

   1. Major surgery within the past 4 weeks (the surgical incision should be fully healed before study drug administration).
   2. Any anticancer therapy within the past 3 weeks before enrollment.
   3. Extended field radiation within the past 4 weeks or limited field radiation within the past 2 weeks before enrollment.
   4. Any investigational drug/device received within the past 4 weeks or 5 times the half-life (whichever is shorter) before enrollment.
3. Previous treatment with TAS-102.
4. Prior treatment with anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death ligand (anti-PD-L1), anti programmed cell death ligand 2, anti-CD137, anti-OX-40, anti CD40, anti cytotoxic T lymphocyte associated antigen-4 antibodies, or any other immune checkpoint inhibitors.
5. Unresolved toxicity of \>=Common Terminology Criteria for Adverse Events version (CTCAE) version 4.03 grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity).
6. Prior events of immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune mediated nephritis and renal dysfunction, immune mediated rash, immune mediated encephalitis, and history of infusion reactions to nivolumab.
7. Known or assumed hypersensitivity to TAS-102 or nivolumab or any of its ingredients, including polysorbate 80-containing infusion.
8. Previous severe hypersensitivity reaction to treatment with another mAb.
9. Pregnant or lactating female.
10. Inappropriate for entry into this study in the judgment of the investigator.