The incidence of colorectal cancer (CRC) increases with older age. Cancer and treatment-related side effects often lead to physical decline, poor treatment adherence, and a lower quality of life. The aim of the present systematic review and meta-analysis was to evaluate the effects of exercise reported by randomized controlled trials (RCTs) on physical function, physical fitness (ie, aerobic capacity, muscle strength) physical activity, and psychological well-being in older patients with CRC undergoing chemotherapy. Eight RCTs with 552 participants were included in the meta-analysis. The mean age across the RCTs was 58.5 years, and 2 RCTs excluded patients aged > 80 years. The meta-analyses showed a low level of evidence for a small beneficial effect of exercise on self-reported physical function (standardized mean difference [SMD], 0.26; 95% confidence interval [CI], 0.04-0.48) and global quality of life (SMD, 0.22; 95% CI, 0.02-0.43) and low level of evidence for a moderate effect of exercise reducing fatigue (SMD, −0.49; 95% CI, −0.79 to −0.19) for patients receiving chemotherapy for CRC. We found no evidence for a beneficial effect of exercise on physical fitness. No adverse events related to the exercise interventions were reported. The evidence for the effect of exercise on physical outcomes and psychological well-being during chemotherapy for patients with CRC and especially for older patients is sparse. However, exercise during chemotherapy for patients with CRC is feasible and safe. We found a moderate to high risk of bias in most of the included studies, small sample sizes, and a low number of included patients. Moreover, all studies had excluded patients with comorbidities or walking impairment, a group of patients who would probably benefit the most from exercise. This positive result requires verification in larger trials of older and frail patients receiving chemotherapy for CRC.