Background: Salvage chemotherapy after progression on immune checkpoint inhibitors (ICIs) was associated with an objective response rate (ORR) of 30% in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We aimed to investigate the efficacy of taxanes + cetuximab (TC) +/- platinum chemotherapy in pts with R/M SCCHN who failed ICIs in palliative setting. Methods: A retrospective study was conducted at 7 French university hospitals. Eligibility criteria were pts treated with ICI for R/M SCCHN, who progressed after treatment with ICI and received TC +/- platinum salvage chemotherapy between August 2017 and December 2021. Clinical and radiological data and outcome were collected from review of medical records. Results: Ninety-nine pts met eligibility criteria: 63 pts received TC and 36 pts received triplet regimen (TR). The median age was 61 years (range 24-78) and 79% of pts were male. Forty-two pts (42%) had platinum-refractory disease (PRD) after multimodal treatment, 13 pts received prior taxanes and 24 pts received prior cetuximab. The median PS at salvage chemotherapy was 1 (range 0-3). ICIs were given as first-line treatment in 70% of pts including those with PRD. The ORR of the entire cohort was 62% (61/99) including 5 complete responses (CR) and the disease control rate was 79% (78/99). The median progression-free survival of the entire cohort was 4.4 months and the median overall survival (OS) was 7.5 months. The 5 pts who had CR as best response are still in remission after a median follow-up of 24 months (range 8-58). The ORR of TC subgroup was 57% (36/63) and the ORR of TR subgroup was 69% (25/36). Furthermore, the ORR in the PRD subgroup of pts was 54% (39/72), and the ORR in the subgroup of pts who were not chemo naïve was 54% (39/72). The ORR in pts who previously received cetuximab was 50% (12/24) vs 75% (49/75) in those who did not. The ORR in pts who previsouly received taxanes was 38% (5/13) vs 65% in those who did not. Finally, the ORR in PRD pts and treated with TR was 50% (7/14) and the ORR in pts who previously received platinum-based treatment or PRD and treated with TR was 55% (11/20). Conclusions: TC +/- platinum chemotherapy was highly effective in pts R/M SCCHN who progressed on ICIs with an ORR of 62% and DCR of 79%. Further investigations are warranted.