Background: Pan added to combination chemotherapy is a preferred first-line therapy for unresectable RAS and BRAF wild type mCRC. Elderly patients may not be suitable for such combination regimens, where FU plus bevacizumab (bev) is used. We therefore investigated two lower intensity pan-containing first-line regimens in an elderly population. Methods: We conducted a prospective, non-comparative, randomized phase 2 study of pan alone (arm A) or pan plus FU (arm B). The study recruited previously untreated patients with unresectable mCRC who were aged 70 years or older; with RAS and BRAF wild type mCRC, and ECOG performance 0-2. Patients were randomized (1:1) to pan 6mg/kg 2 weekly or pan plus FU 400 mg/m2 bolus; leucovorin 200mg/m2; FU 2400mg/m2 46-hour infusion 2 weekly. Treatment was continued until progression. The primary study endpoint was 6-month progression-free survival (PFS). Secondary endpoints were: overall survival (OS), response rate (RR), feasibility of a composite geriatric assessment (EORTC QLQ-C30, symptoms, Mini-Mental State Examination, timed 20-metre walk, Charlson Co-morbidity Index, weight loss/arm circumference), toxicity and overall treatment utility (OTU)- a composite measure of treatment benefit based on radiological response, clinician-assessed clinical progress, toxicity and patient-reported treatment impact and worth. The planned sample size was 40 patients per arm, based on an expected PFS of 73% at 6 months. Results: 36 of the planned 80 patients (arm A n=19, arm B n=17) were randomized between June 2018 and June 2021. Recruitment was hampered by a high rate of RAS and BRAF mutations and COVID19. Median age was 79 and 80 years, left sided primary in 74% and 82% and ECOG 0/1 in 89% and 100% in arms A and B, respectively. Median follow up was 36 months. 6-month PFS was 63% (95% CI 38-80%) in arm A and 82% (95%CI 55%-94%) in arm B. Median OS was 21 months in arm A (95%CI 13-31) and 28 (95%CI 14-39) months in arm B. RR was 47% and 65% in arms A and B respectively. Baseline comprehensive geriatric assessments were fully completed in >80% of patients. At week 16, OTU was categorized as good in 92% (arm A) and 90% (arm B) of patients.Rates of adverse events and serious adverse events were similar between the arms. Conclusions: 6-month PFS in both arms was consistent with the hypothesized rate of 73% achieved with FU/bev, whilst the rate was numerically higher for arm B. Baseline comprehensive geriatric assessments were feasible and OTU was high in both arms. Both treatment arms might be suitable first-line options in appropriately selected patients. Acknowledgements: Partial funding and panitumumab provided by AMGEN. MONARCC was partially funded and sponsored by AGITG; co-ordinated by NHMRC CTC, University of Sydney. Clinical trial information: ACTRN 12618000233224.