The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5 -29.2%) and 49% (95% CI, 42.2 -55.8%), respectively (P ¼ 0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the nonmucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27 -3.31; P ¼ 0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05 -2.40; P ¼ 0.0267), together with performance status ECOG 2, number of metastatic sites X2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.