Background: Physical activity (PA) is a modifiable health behaviour in patients with colorectal cancer (CRC). Knowing the possible predictors of PA will contribute to producing physical and psychological benefits for CRC patients. Objective: To investigate the factors that influence PA in patients with CRC. Methods: This cross-sectional study was conducted with 47 participants with CRC. Demographic and clinical characteristics, neuropathic pain (Douleur Neuropathique 4 (DN4)), peripheral muscle strength (knee extensor and flexor, hip extensor and flexor, and ankle dorsiflexor muscle strength), balance (Balance Master System (BMS) and Berg Balance Scale (BBS)), fatigue (Brief Fatigue Inventory (BFI)), PA (International PA Questionnaire Short Form (IPAQ-SF)), and quality of life (36-item Short Form Health Survey (SF-36)) were evaluated. Multiple linear regression analysis was used to determine the variables that have the greatest influence on PA. Results: IPAQ-SF score had moderate correlations with knee extensor muscle strength (r = 0.310, p = 0.034), BBS (r = 0.361, p = 0.013), and limit of stability test (movement velocity) score (r = 0.385, p = 0.008), BFI- severity of fatigue (r = − 0.488, p = 0.001), impact of fatigue on daily functioning (r = − 0.421, p = 0.003), and the SF-36 sub-parameters (role limitations due to physical health problems, physical functioning, general health perceptions and vitality) (p < 0.05). Role limitations due to physical problems, knee extensor muscle strength, and severity of fatigue had the greatest influence on PA in patients with CRC with explaining 43% of the variance in PA. Conclusions: This study suggests that quality of life, knee extensor muscle strength, and fatigue have the greatest influence on PA in patients with CRC.