This is a Phase Ⅱ/Ⅲ study. The purpose of this study is to evaluate the efficacy and safety of RC148 combined with chemotherapy for the first-line treatment of unresectable metastatic colorectal cancer (CRC)

Primary objective in Phase II: To preliminarily evaluate the efficacy of RC148 combined with chemotherapy as first - line treatment for unresectable or metastatic CRC.

Primary objective in Phase III: To evaluate the efficacy of RC148 combined with chemotherapy compared with bevacizumab combined with chemotherapy as first - line treatment for unresectable or metastatic CRC.

Inclusion Criteria:

1. Voluntarily agree to participate in the study, sign the informed consent form, and be able to comply with the study protocol.
2. Aged 18-75 years old (including 18 years old and 75 years old).
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
4. Expected survival period ≥ 12 weeks.
5. At least one measurable lesion according to RECIST v1.1 criteria.
6. Histologically or cytologically confirmed colorectal adenocarcinoma, judged by the investigator as unsuitable for curative treatment, and no prior systemic anti-tumor treatment in the recurrent or metastatic stage.
7. Subjects must be able to provide tumor tissue samples for biomarker detection.
8. Adequate bone marrow, liver, kidney, and coagulation function.
9. Female subjects of childbearing potential must agree to use at least one medically approved contraceptive method during the study treatment and for 6 months after the end of the study treatment, and must have a negative blood pregnancy test within 7 days before study enrollment; male subjects must agree to use at least one medically approved contraceptive method during the study treatment and for 6 months after the end of the study treatment.

Exclusion Criteria:

1. Known to have microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR).
2. Imaging shows obvious tumor necrosis or cavitation, and the investigator judges that participation in the study may increase the risk of bleeding.
3. Subjects with brain metastases.
4. Toxicities from prior anti-tumor therapy have not recovered to ≤ grade 1 according to NCI-CTCAE v6.0.
5. Known hypersensitivity or delayed-type allergy to any component of the study drug or similar drugs.
6. Subjects with refractory nausea and vomiting, chronic gastrointestinal diseases, or other diseases that may interfere the adequate absorption, distribution, metabolism, or excretion of oral drugs.
7. Subjects with acute, chronic, or symptomatic infections.
8. Subjects with diagnosed or suspected interstitial lung disease (ILD), drug-related pneumonia, radiation pneumonitis, severe impairment of lung function, or other lung diseases.
9. Subjects with active inflammatory bowel disease, a history of gastrointestinal perforation and/or fistula, or clinical symptoms of gastrointestinal obstruction.
10. Subjects with severe arterial/venous thromboembolic events within 6 months before randomization.
11. Active gastrointestinal bleeding, hemoptysis, peptic ulcer, or hemorrhagic events requiring intervention within 28 days before randomization; or presence of severe esophagogastric varices or epistaxis.
12. Presence of symptomatic or intervention-requiring third-space effusions.
13. Subjects with active or previously diagnosed autoimmune diseases that may recur.
14. History of other invasive malignant tumors within 5 years before randomization, or presence of any residual evidence of previously diagnosed malignant tumors.
15. Subjects who are pregnant, lactating, or planning to become pregnant.

The Phase II of this study is designed to be a randomized and open - label trial. The Phase III is a randomized and double - blind study, in which neither the researchers nor the subjects know the type of investigational drug given in addition to chemotherapy.