Background: Unplanned delays are common during FOLFOX chemotherapy, and cytopenias (neutropenia and/or thrombocytopenia) are the most common cause of delays. We evaluated a novel, provider-driven FOLFOX dose-adjustment algorithm designed to reduce unplanned delays while maintaining chemotherapy dose intensity. Methods: We conducted a pragmatic, single-arm clinical trial to evaluate the FOLFOX dose adjustment algorithm (NCT04526886). The algorithm prescribed graded chemotherapy dose reductions without delay on day 1 of cycles 2-6 for patients with an absolute neutrophil count (ANC) of 750 to 1499/microL and/or a platelet count of 50 to 99 K/microL. The algorithm prescribed a delay when ANC was less than 750 or platelet count was less than 50 on day 1 of cycles 2-6. Chemotherapy dose adjustments and delays for reasons other than cytopenias were at the discretion of the treating provider. Patients receiving initial treatment with FOLFOX chemotherapy (with or without concomitant monoclonal antibodies) were eligible. Subjects received standard chemotherapy doses in cycle 1 (bolus 5-FU 400 mg/m2, oxaliplatin 85 mg/m2, and infusional 5-FU 2400 mg/m2/46 hours). Use of granulocyte colony stimulating factor (GCSF) was not permitted, except for patients who had already experienced an unplanned delay. The primary outcome was any unplanned delay prior to completion of day 1 of cycle 6 of chemotherapy (with an interval of >18 days between cycles.) We tested whether the incidence of any unplanned delay was less than the historical rate of 43%, using a one-sample test of proportions. Chemotherapy relative dose intensity (RDI) over cycles 1-6 was a key secondary outcome. Results: 48 of 54 enrolled subjects were evaluable. The median age was 66, and 50% were female. The most common primary cancer sites were colorectal (n = 31) and gastroesophageal (n = 12). Metastatic cancer was present in 67%, and 35% received a concurrent monoclonal antibody. Sixteen of 48 subjects had any unplanned delay before completing cycle 6 (33%, 95% CI 0.22-0.47, p = 0.08 for comparison with historical proportion of 43%), and 7 subjects had any cytopenia-related delay (15%, CI 0.07-0.27). Twenty-one subjects (44%) had one or more algorithm-driven chemotherapy dose reductions without a delay, and 8 cycles were delivered without delay with an ANC of 750-999 (without GCSF). The mean (median) chemotherapy RDIs were: bolus 5-FU, 65% (67%); oxaliplatin, 85% (90%); and infusional 5-FU, 92% (97%). Conclusions: The 33% observed incidence of any unplanned chemotherapy delay was nominally but not significantly lower than the historical rate of 43%. The incidence of any cytopenia-related delay was 15%, lower than the historical rate of >30%. Further refinement and evaluation of the FOLFOX dose adjustment algorithm may help to reduce unplanned delays and their attendant disruptions and costs for patients and providers. Clinical trial information: NCT04526886.