The severe operation conditions in nuclear reactors, such as highly turbulent coolant flow, high temperatures and excessive irradiation doses, can compromise the structural integrity of nuclear fuel bundles. Specifically, the irradiation doses influence the microstructure of the material in terms of segregation and precipitation in addition to swelling. This leads to changes in the mechanical properties of the material and consequently, the dynamic characteristics will be altered. The current study presents a fully-coupled, three-dimensional, numerical, structural model that takes into account the irradiation effects on fuel bundle material. A constitutive model that describes the thermal and irradiation effects on the mechanical properties is utilized. This constitutive model is integrated in an in-house finite element code that is capable of predicting the dynamics of fuel bundles including the nonlinear material, contact dynamics, and various fluid and acoustic excitation forces. This model is utilized to predict the response of a CANDU fuel bundle under turbulence excitation, motion-dependent forces, and acoustic pressure pulsations generated by the heat transport pumps. The fuel-to-fuel and fuel-to-pressure tube contact dynamics are also included using the single point contact method (SPC). The dynamic response of the fuel bundle along with the associated impact forces and work rates are predicted over a range of flow velocities that are typical to those in an actual CANDU power plant. The results indicate that the location of the fuel channel inside the calandria tube may exacerbate the mechanical stresses on the fuel bundle endplates, which could compromise their structural integrity.