Inclusion Criteria:

          -  Has a histologically confirmed diagnosis of Stage IV CRC adenocarcinoma (as defined by
             American Joint Committee on Cancer [AJCC] version 8)

          -  Has locally confirmed dMMR/MSI-H

          -  Has a life expectancy of at least 3 months

          -  Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 at
             screening and within 3 days before Cycle 1 Day 1

          -  Female participants are eligible to participate if not pregnant or breastfeeding, and
             not a woman of childbearing potential (WOCBP), or if a WOCBP then is using a
             contraceptive method that is highly effective or is abstinent on a long-term and
             persistent basis, during the intervention period and for at least 120 days after the
             last dose of study intervention

          -  Has measurable disease per RECIST 1.1 as assessed by BICR

          -  Has adequate organ function

        Cohort A:

          -  Has been previously treated for their disease and radiographically progressed per
             RECIST 1.1 on or after or could not tolerate standard treatment, which must include
             all of the following agents if approved and locally available in the country where the
             participant is randomized:

               -  Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as
                  equivalent to fluorouracil in prior therapy)

               -  With or without an anti-vascular endothelial growth factor (VEGF) monoclonal
                  antibody (e.g., bevacizumab)

               -  At least one of the anti-epidermal growth factor receptor (EGFR) monoclonal
                  antibodies (cetuximab or panitumumab) for rat sarcoma viral oncogene homolog
                  (RAS) wild-type participants with left-sided tumors

          -  Must not have had prior exposure to PD-1 or PD-L1 therapies as treatment for this
             disease

        Cohort B:

        - Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for
        this disease

        Cohort C:

          -  Has radiographically progressed on-treatment with an anti-PD-1 monoclonal antibody
             (mAb) administered either as monotherapy or in combination with other therapies

          -  Has had 0 to 1 prior systemic fluoropyrimidine based chemotherapy regimens

          -  Must not have been treated in Cohort A

        Exclusion Criteria:

          -  Has received prior therapy with an agent directed to another stimulatory or
             coinhibitory T-cell receptor

          -  Has received prior systemic anticancer therapy including investigational agents within
             4 weeks before the first dose of study intervention

          -  Has not recovered adequately from a surgery procedure, and/or has any complications
             from a prior surgery before starting study intervention

          -  Has received prior radiotherapy within 2 weeks of start of study intervention

          -  Has received a live or live-attenuated vaccine within 30 days before the first dose of
             study intervention

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks before the first dose of
             study intervention

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study medication

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 2 years

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab, quavonlimab and/or any of
             their excipients

          -  Has an active autoimmune disease that has required systemic treatment in past 2 years
             (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs)

          -  Has a history of (noninfectious) pneumonitis that required steroids or has current
             pneumonitis

          -  Has an active infection requiring systemic therapy (e.g., tuberculosis, known viral or
             bacterial infections, etc.)

          -  Has a known history of Human Immunodeficiency Virus (HIV) infection

          -  Has known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive
             and/or detectable Hepatitis B Virus [HBV] deoxyribonucleic acid [DNA]) or active
             Hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected or
             anti-HCV antibodypositive) infection

          -  Is pregnant, or breastfeeding, or expecting to conceive children within the projected
             duration of the study, starting with the Screening Visit through 120 days after the
             last dose of study intervention

          -  Has had an allogenic tissue/solid organ transplant