BACKGROUND: Adjuvant chemotherapy plays important role in the comprehensive treatment of patients with stage III colorectal cancer. However, there is few molecular markers for predicting the therapeutic effect. OBJECTIVE: To identify factors that could predict adjuvant chemotherapy benefits in patients with stage III colorectal cancer. METHODS: The medical records of 294 patients were reviewed and analyzed using the Kaplan-Meier method and Cox analysis. RESULTS: Lower CA125 (⩽ 35 u/ml, P= 0.0015) serum levels, stage IIIa (P= 0.0027), 1-3 positive lymph nodes (P= 0.0256), negative vascular invasion (P= 0.0215), lower CA199 (⩽ 27 u/ml, P= 0.0038) serum levels, and wild-type BRAF status (P= 0.0125) were significantly associated with a higher 2-year DFS rate in patients with stage III colorectal cancer. However, in multivariate COX analysis, the association remained significant only for CA125 levels (vs. ⩽ 35 u/ml group, HR 3.341; 95% CI, 1.198-9.316; P= 0.0212), vascular invasion (vs. negative vascular invasion, HR, 2.349; 95% CI, 1.227-4.499; P= 0.01), and BRAF (V600E) (vs. wild Braf, HR, 7.794; 95% CI, 1.867-32.531; P= 0.0049). CONCLUSION: Lower CA125 serum levels, negative vascular invasion, and wild-type BRAF status were significantly associated with improved 2-year DFS rates among patient with stage III disease who received adjuvant chemotherapy.