The FIRE-6 avelumab study (AIO KRK-0118) was performed in RAS-wild-type mCRC patients. This multi-center single-arm study tested the efficacy of avelumab maintenance during 1st-line therapy after 4 cycles of induction treatment with FOLFIRI plus cetuximab (FOLFIRI/Cet) followed by 4 cycles of combination treatment using FOLFIRI/Cet plus avelumab. Subsequently, treatment was continued with avelumab until progression or intolerable toxicity. Patients received FOLFIRI (irinotecan plus 5-FU/FA) every two weeks plus cetuximab weekly at the standard dosing schedule. After 4 cycles of therapy, avelumab (10mg/kg q2w) was added to FOLFIRI/Cet and continued for another 4 cycles before maintenance with avelumab monotherapy was started. Median progression-free survival (PFS) according to RECIST v1.1 was evaluated as primary endpoint. With a target PFS ≥ 12.88 months, the study was designed to reject the null hypothesis of PFS ≤8.0 months with a power of 80% at a one-tailed significance level of 0.025. Secondary endpoints included ORR, OS, safety, and tolerability. From November 2019 to June 2021, 57 patients were treated within the study protocol. Treatment with FOLFIRI/Cet plus avelumab was well tolerated and no new or unexpected toxicities were observed. Median PFS was 7.0 months in 47 evaluable patients. Overall response rate was 73.2% with a disease control rate of 87.5%. Median time on avelumab maintenance was 1.9 months with a range up to 15.6 months. Median OS was not reached at the time of the latest data cut-off with only 21.4% of OS events had occurred. With a median PFS of 7.0 months, FIRE-6 avelumab did not reach its pre-specified endpoint. Avelumab maintenance after FOLFIRI/Cet therefore is not effective to postpone disease progression after FOLFIRI/Cet induction therapy in first-line RASwt mCRC patients. Some long-term responders are present and will be further analyzed. FOLFIRI/Cet plus avelumab is safe and feasible as no unexpected toxicities occurred. FIRE-6 avelumab confirms the efficacy with respect to tumor response and disease control of FOLFIRI plus cetuximab as first-line treatment of patients with RAS wild-type mCRC.