Objective To explore the efficacy and safety of cadonilimab combined with bevacizumab biosimilar and chemotherapy (FOLFOX/FOLFIRI) as first-line treatment for RAS-mutated, microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Methods Using a prospective, single-arm exploratory study, patients with RAS-mutated, MSS mCRC who visited the People's Hospital of Inner Mongolia Autonomous Region from April 2024 to April 2025 were selected. They received chemotherapy with 250 mg of cadonilimab plus 5-7.5 mg/kg of bevacizumab and FOLFOX/FOLFIRI regimens. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), as well as PFS rates at 3, 6, and 12 months and the incidence of adverse reactions. Additionally, the quality of life of patients before and after treatment was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) scale. Results A total of 32 patients were enrolled, with an ORR of 53.1% and a DCR of 96.9% after treatment. The median PFS was 11.4 months, with a 95% confidence interval (CI) of (9.6, 13.5) months. The median overall survival was not reached. The PFS rates at 3, 6, and 12 months were 96.9%, 90.6%, and 46.9%, respectively. Common adverse reactions after treatment included myelosuppression, vomiting/nausea, hand-foot syndrome, and endocrine toxicity. Most adverse reactions were grade 1 to 2, with a few being grade 3. No grade 4 to 5 adverse reactions occurred. Subgroup analysis showed that patients with an Eastern Cooperative Oncology Group (ECOG) score ≥ 2, primary cancer site in the right-sided colon, and concurrent liver metastasis had significantly poorer prognosis (P < 0.05). The EORTC QLQ-C30 scale assessment showed improvements in patients' overall health status and functional domains, with core symptoms significantly alleviated. Conclusion In the first-line treatment of RAS-mutated, MSS mCRC, the treatment regimen combining cadonilimab with bevacizumab analogues and chemotherapy showed certain benefits in key efficacy endpoints such as ORR and PFS, with manageable overall safety. No new or intolerable toxicities were observed, and it has advantages for patients with ECOG scores of 0-1, with a primary tumor in the left-sided colon, and without liver metastasis. Due to limitations such as a small sample size and short follow-up time, large-scale clinical studies should be conducted in the future for further exploration and verification.

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