• Have unresectable histologically confirmed adenocarcinoma of the colon or rectum.

• Have confirmed non-microsatellite instability-high (non-MSI-H)/pMMR mCRC per Food and Drug Administration (FDA)/European Commission (EC) approved test or based on local testing.

• Have measurable disease defined by RECIST v1.1.

• Must provide a tumor tissue sample (formalin-fixed, paraffin-embedded or tissue slides) collected before C1D1 for enrollment. A newly obtained tumor sample is preferred. If it is not feasible to obtain a recent tumor sample, participants can provide archival tumor tissue (less than 2 years prior treatment).

• Have Eastern Cooperative Oncology Group Performance Status of 0 or 1.

• Have a life expectancy of ≥12 weeks.

• Have an adequate organ and bone marrow function within ≤7 days of Day 1 as defined in the protocol.

• Have had an adequate previous treatment washout period before randomization/enrollment as defined in the protocol.

• Have received at least two previous lines of therapy for metastatic disease.

• Have progressed following first-line chemotherapy as specified in the protocol.

• Have not received prior systemic therapy for MSS/pMMR mCRC. Participants who received chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease in the neoadjuvant or adjuvant setting are eligible for the study if therapy was completed at least 6 months prior to initiation of study treatment.

⁃ Other cohort-specific inclusion criteria apply.