Inclusion Criteria:

          -  Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.

          -  Histologically- or cytologically-confirmed mCRC.

          -  Microsatellite instability-high (MSI-H) / mismatch repair-deficient (dMMR) tumors must
             have received prior therapy with pembrolizumab, nivolumab, or other programmed cell
             death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway blocker, and must
             have progressed on that therapy.

          -  Meeting the protocol definition of TNmCRC assessed in the screening blood test.

          -  mCRC currently not amenable to surgical intervention due to either medical
             contraindications or non-resectability of the tumor.

          -  Measurable disease according to RECIST v1.1, and willingness to undergo a total of 2
             biopsies of a primary or metastatic tumor site(s) considered safely accessible for
             biopsy.

          -  Must have received at least 2 prior regimens of standard chemotherapy for mCRC and
             must have been refractory to or failed (includes intolerance to) those regimens. Prior
             standard chemotherapy may not have included TAS-102 or regorafenib, but must have
             included agents as specified in the protocol.

          -  "Acquired" resistance to commercially available anti-EGFR mAbs approved for the
             treatment of mCRC must have:

               1. Received treatment with an anti-EGFR for ≥16 weeks

               2. Progressive disease (PD) documented by imaging or clinical findings less than or
                  equal to 6 calendar months after cessation of previous anti-EGFR mAb treatment

               3. No more than 6 calendar months from last dose of previous anti-EGFR mAb treatment
                  to date of consent for this trial (regardless of the line of therapy in which it
                  was used)

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

          -  Not of childbearing potential or who agree to use a highly effective method of
             contraception during the study beginning within 2 weeks prior to the first dose and
             continuing until 3 months after the last dose of study drug.

        Exclusion Criteria:

          -  Women who are pregnant or lactating or intending to become pregnant before, during, or
             within 3 months after the last dose of study drug.

          -  Prior history of specific mutations (specified in the protocol) in the tumor at the
             time of any previous assessment.

          -  Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal
             cord compression; patients with any of these not controlled by prior surgery or
             radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment
             is required

          -  An active second malignancy or history of another malignancy within the last 5 years,
             with exceptions.

          -  Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism
             (PE) within 4 weeks prior to first administration of study drug unless adequately
             treated and considered by the Investigator to be stable.

          -  Active uncontrolled bleeding or a known bleeding diathesis

          -  Known clinically significant cardiovascular disease or condition.

          -  Non-healing wounds on any part of the body.

          -  Significant gastrointestinal abnormality.

          -  Skin rash > Grade 1 from prior anti-EGFR therapy at the time of randomization.

          -  Unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy

        Drugs and Other Treatments Exclusion Criteria:

          -  Prior treatment with TAS-102 or regorafenib

          -  Any antineoplastic agent for the primary malignancy (standard or investigational)
             without delayed toxicity within 4 weeks prior to first administration of IMP and
             during study with exceptions

          -  Any other investigational treatments within 4 weeks prior to and during study;
             includes participation in any medical device or other therapeutic intervention
             clinical trials

          -  Radiotherapy as specified in the protocol

          -  Immunosuppressive or systemic hormonal therapy (> 10 mg daily prednisone equivalent)
             within 2 weeks prior to first administration of IMP and during study; allowed
             therapies are specified in the protocol.