This is a multicentre, open-label, parallel arms, phase IIII study that randomises patients with locally recurrent rectal cancer in a 1:1 ratio to receive either induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm)

Inclusion Criteria:

• 18 years or older
• Confirmed locally recurrent rectal cancer after total or partial mesorectal resection for rectal or distal sigmoidal cancer either by histopathology ór clinically proven (evidence on imaging in combination with clinical findings, with consensus in MDT)
• Resectable disease determined by magnetic resonance imaging (MRI) or deemed resectable after neoadjuvant treatment with chemoradiotherapy.
• WHO performance score 0-1
• Written informed consent

Exclusion Criteria:

• Radiological evidence of metastatic disease (e.g. liver, lung) at time of randomisation or in the six months prior to randomisation.
• Known homozygous DPD deficiency
• Any chemotherapy in the past 6 months.
• Any contraindication for the planned chemotherapy, as determined by the medical oncologist.
• Radiotherapy in the past 6 months for primary rectal cancer.
• Any contraindication for the planned chemoradiotherapy, as determined by the medical oncologist and/or radiation oncologist.
• Any contraindication for surgery, as determined by the surgeon and/or anaesthesiologist.
• Concurrent malignancies that interfere with the planned study treatment or the prognosis of resected LRRC.

Participant-level datasets and statistical codes will become available upon reasonable request after the results of the study have been published.

The full protocol and Dutch informed consent forms are publicly accessible after approval of the medical ethics committee.