Background <p>Capecitabine and Oxaliplatin (CAPOX) chemotherapy is a standard treatment for stage 2/3 colorectal cancer but is associated with dose-limiting toxicities. Short-term fasting may protect healthy cells from chemotherapy-related side effects via differential stress resistance. However, it is not known whether it is possible to recruit to a trial of short-term fasting in this population, or whether participants would adhere to the intervention. The aim was to test the feasibility and acceptability of a pre-chemotherapy, 36-h, water-only fast prior to the first three cycles of chemotherapy in people receiving CAPOX chemotherapy for stage 2/3 colorectal cancer.</p> Methods <p>A two-armed randomised controlled feasibility trial with an embedded qualitative interview study conducted in two NHS foundation trust hospital sites in England. Participants were randomly allocated, in a 1:1 ratio using random permuted blocks, by a secure online randomisation system, to either a 36-h fast immediately prior to chemotherapy administration or standard dietary advice. The intervention was delivered during chemotherapy cycles 1–3. Primary outcomes were adherence, recruitment, retention, data completion, and acceptability. Secondary outcomes included chemotherapy side effects, quality of life, metabolic and inflammatory markers, appetite, and sarcopenia.</p> Results <p>Seventy-nine patients were screened, of whom44 were eligible. Twelve consented and were randomised (intervention: <i>n</i> = 6; control: <i>n</i> = 6). The retention rates for chemotherapy cycles 1, 2, and 3 were 100%, 83%, and 83% for the intervention group and 100%, 100%, and 100% for the control. Five out of six participants adhered to the fast. The trends observed in levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins 2 and 3 (IGFBP-2 and IGFBP-3) were consistent with effective fasting. Qualitative findings indicated that fasting was achievable but sometimes perceived as an additional burden alongside chemotherapy. Recruitment challenges were influenced by site-level factors, including competing priorities, COVID-19-related disruptions, and perceptions of the intervention.</p> Conclusion <p>The SWiFT study was feasible to deliver and adherence to the fast was high. In a future definitive trial, success in recruitment appears to depend more on specific local factors rather than the intervention being unattractive to most potential participants.</p> Trial registration <p>ISRCTN, ISRCTN17994717, registered 23 October 2018, <a href="https://www.isrctn.com/ISRCTN17994717">https://www.isrctn.com/ISRCTN17994717</a></p>