Abstract Purpose Colorectal cancer (CRC) risk is associated with modifiable lifestyle factors including smoking, physical inactivity, Western diet, and excess body weight. The impact of lifestyle factors on survival is less known. A cohort study was conducted to investigate the combined effects of a healthy lifestyle and body mass index on prognosis following CRC diagnosis. Methods Treatment and follow-up data were collected from the patient files of 1098 participants from the Colorectal cancer low-risk study cohort including stage I-III CRC patients. A healthy lifestyle and BMI (HL) score was computed using self-reported data on smoking status, physical activity, adherence to a Mediterranean diet pattern, and BMI, and divided into four categories ranging from least to most healthy. Survival analyses were performed to assess recurrence-free survival and overall survival across categories of exposure, using the Kaplan–Meier method and Cox proportional hazards models adjusted for age, sex, and educational level. Results Among 1098 participants with stage I-III CRC, 233 (21.2%) had an HL score of 0–1 (least healthy), 354 (32.2%) HL score of 2, 357 (32.5%) HL score of 3 and 154 (14.0) HL score 4 (most healthy). Patients with the healthiest lifestyle (HL score 4) compared to the least healthy (HL score 0–1) had an improved recurrence-free survival (HL 4 vs HL 0–1, HRadj 0.51 (95% CI 0.31–0.83) and overall survival (HL 4 vs HL 0–1, HRadj 0.52 (95% CI 0.38–0.70). Conclusion Adherence to a healthy lifestyle may increase the recurrence-free and overall survival of patients with stage I–III CRC.