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Exercise and physical activity have been shown to be strongly associated with a decreased incidence rate of various chronic diseases especially numerous human malignancies. A huge number of clinical trials and meta-analysis have demonstrated that exercise is significantly effective in lowering the risk of colorectal cancer. In addition, it is suggested as an effective therapeutic modality against this cancer type. Therefore, in this review, we will review comprehensibly the effects of exercise in preventing, treating, and alleviating the adverse effects of conventional therapeutic options in colorectal cancer. Moreover, the possible mechanisms underlying the positive effects of exercise and physical activity in colorectal cancer, including regulation of inflammation, apoptosis, growth factor axis, immunity, epigenetic, etc. will be also discussed.