Purpose <p>Unplanned delays are common during FOLFOX chemotherapy. We evaluated a novel FOLFOX dose modification algorithm designed to reduce unplanned delays while maintaining dose intensity.</p> Methods <p>We conducted a pragmatic, single-arm clinical trial to evaluate PAGODA, a proactive graduated dose modification algorithm for FOLFOX chemotherapy (NCT04526886). The algorithm prescribes chemotherapy dose reductions and delays based on absolute neutrophil count (ANC) and platelet count. Patients receiving FOLFOX-based chemotherapy were eligible. Participants received standard chemotherapy doses in cycle 1 (bolus 5-FU 400&#xa0;mg/m², oxaliplatin 85&#xa0;mg/m², and infusional 5-FU 2400&#xa0;mg/m²/46&#xa0;h). The primary outcome was unplanned delay prior to cycle 6 (&gt; 18&#xa0;days between cycles). We compared the incidence of unplanned delay against the historical proportion of 43%. Relative dose intensity (RDI) was a key secondary outcome.</p> Results <p>There were 48 evaluable participants. The median age was 66, and 50% were female. The most common primary cancer sites were colorectal (<i>n</i> = 31) and gastroesophageal (<i>n</i> = 12). Sixteen of 48 subjects had any unplanned delay before completing cycle 6 (33%, 95% CI 0.22–0.47, <i>p</i> = 0.18 for comparison with the historical proportion) and seven subjects had any cytopenia-related delay (15%, CI 0.07–0.27). Seven cycles were delivered without delay with an ANC of 750–999/µl. The mean chemotherapy RDIs were: oxaliplatin, 86%; infusional 5-FU, 92%; and bolus 5-FU, 65%.</p> Conclusions <p>The PAGODA dose modification algorithm was safe and was associated with a low rate of cytopenia-related delays. Further intervention refinement and testing may help to reduce unplanned delays and attendant time toxicity.</p> Trial registration <p>Registered at ClinicalTrials.gov on August 21, 2020. ClinicalTrials.gov ID: NCT04526886.</p>