The primary purpose of this study is to evaluate XL092 + atezolizumab versus regorafenib in participants with microsatellite stable/microsatellite instability low (MSS/MSI-low) metastatic colorectal cancer (mCRC) who have progressed during, after or are intolerant to standard-of-care (SOC) therapy.

Key Inclusion Criteria:

• Participants with histologically or cytologically confirmed adenocarcinoma of the colon or rectum.

  • Documented rat sarcoma (RAS) status (mutant or wild-type [WT]), by tissue-based analysis.
  • Documented NOT to have microsatellite instability-high (MSI-high) or mismatch repair deficient (dMMR) CRC by tissue-based analysis.

• Has received SOC anticancer therapies as prior therapy for metastatic CRC and has radiographically progressed, is refractory or intolerant to these therapies.

  • Systemic SOC anticancer therapy if approved and available in the country where the participant is randomized.
  • Radiographic progression during treatment with or within 4 months following the last dose of the most recent approved SOC chemotherapy regimen.

• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by the Investigator.

• Available archival tumor biopsy material. If archival tissue is unavailable, must provide fresh tumor tissue biopsy prior to randomization.

• Recovery to baseline or ≤ Grade 1 severity (common terminology criteria for adverse events [CTCAE] version 5) from adverse events (AEs) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• Adequate organ and marrow function.

• Fertile participants and their partners must agree to use highly effective methods of contraception during the course of the study and after the last dose of treatment.

• Females of childbearing potential must not be pregnant at screening.

Key Exclusion Criteria:

• Prior treatment with XL092, regorafenib, trifluridine/tipiracil, or programmed cell death protein-1/and its ligand (PD-L1/PD-1) targeting immune checkpoint inhibitors (ICIs).
• Receipt of a small molecule kinase inhibitor (including investigational agents) within 2 weeks before randomization.
• Receipt of any type of anticancer antibody therapy, systemic chemotherapy, or hormonal anti-cancer therapy within 3 weeks (or bevacizumab within 4 weeks) before randomization.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before randomization.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before randomization.
• Has uncontrolled, significant intercurrent or recent illness.
• Major surgery (example, gastrointestinal (GI) surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization.
• Systemic treatment with, or any condition requiring, either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 milliseconds (ms) within 10 days before randomization.
• History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
• Pregnant or lactating females.
• Inability to swallow study treatment formulation, inability to receive IV administration, or presence of GI condition that might affect the absorption of study drug.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• Any other active malignancy or diagnosis of another malignancy within 2 years before randomization. Exceptions are noted in the protocol.
• Administration of a live, attenuated vaccine within 30 days before randomization.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.