In the last decades, more efforts are focused on the prevention and treatment of malignant diseases, given the increase in all cancers incidence A lifestyle change, including healthy eating habits and regular physical activity, has significantly impacted colorectal cancer prevention. The effect of dose-dependent physical activity on mortality and recurrence rates of colorectal carcinoma has been unequivocally demonstrated in observational studies. However, clear recommendations are not available on the frequency, duration, and intensity of exercise in patients with colorectal cancer due to the lack of evidence in randomized clinical trials. Regarding pathophysiological mechanisms, the most plausible explanation appears to be the influence of physical activity on reducing chronic inflammation and insulin resistance with a consequent positive effect on insulin growth factor 1 signaling pathways.