This open label study is therefore proposed to examine the combination of chemoradiation with Selinexor, a SINE XPO1 antagonist, that is being evaluated in Phase 1 studies in solid and hematological malignancies and that has shown single agent activity in heavily pretreated patients with CRC. The long-term goal of the project Is to establish a new treatment for patients with rectal cancer that will improve their cure rate and lengthen their overall survival.